Regioselectivity in the ene reaction of singlet oxygen with ortho-prenylphenol derivatives

Article abstract of DOI:10.1016/S0040-4020(03)00733-6

The ene reaction of singlet oxygen with prenylated dihydroxyacetophenones led to the 2-hydroperoxy-3-methylbut-3-enyl derivatives as the major product. This original regioselectivity outlined a new effect, in competition with the previously established la

Full text of DOI:10.1016/S0040-4020(03)00733-6

Tetrahedron 59 (2003) 5091–5104
Regioselectivity in the ene reaction of singlet oxygen with
ortho-prenylphenol derivatives
a
a
b
Jean-Jacques Helesbeux,a Olivier Duval,a David Guilet, Denis Seraphin, David Rondeau
,
*
´
and Pascal Richommea,b
a
´
´
SONAS, UFR des Sciences Pharmaceutiques et Ingenierie de la Sante, 16 Bd Daviers, 49100 Angers, France
bSCAS, UFR Sciences, 2, Bd Lavoisier, 49045 Angers Cedex 01, France
Received 23 January 2003; revised 19 March 2003; accepted 30 April 2003
Abstract—The ene reaction of singlet oxygen with prenylated dihydroxyacetophenones led to the 2-hydroperoxy-3-methylbut-3-enyl
derivatives as the major product. This original regioselectivity outlined a new effect, in competition with the previously established large
group non-bonding effect. The oxidation products distribution could be explained by a stabilising interaction between the phenolic hydrogen,
ortho to the prenyl side chain, and the perepoxide intermediate. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
also prepared a series of prenylated monophenolic deriva-
tives in order to enlarge the scope of our work on the
Schenck ene reaction of singlet oxygen with ortho-
prenylphenols. Yields, reported in Table 1, were not
optimised. In each experiment, an important part of starting
material was recovered after purification of the crude
product over column chromatography.
As part of our continuous research on bioactive natural
product synthesis, we recently reported the first results of a
study dealing with a new and selective access to ortho-(2-
hydroxy-3-methylbut-3-enyl)phenols derivatives by direct
photoxygenation of ortho-prenylphenol precursors.1 Since
the total synthesis of natural prenylated coumarins was
particularly difficult, acetophenonic derivatives were chosen
as simplified models in this preliminary study.
For the photooxidation step, we chose the smoothest
experimental conditions which have been previously
reported. Thus, singlet oxygen was generated at 2308C in
CH2Cl2 in the presence of tetraphenylporphin (TPP) as the
Furthermore an original oxidation products distribution was
observed in the ene reaction of singlet oxygen with the
prenyl side chain. The main issues of this paper is to report
the full data of our preceding work and to elucidate the
regioselective character of the Schenck reaction with the
prenyl appendage.
photosensitizer.
The
photooxygenation–reduction
sequence, applied to 1, furnished a mixture of secondary
and tertiary allylic alcohols in an 93% overall yield,
determined by 1H NMR spectroscopy (Scheme 2). This
result proved the high chimioselectivity of the ene reaction
towards the prenyl group, although phenolic functions were
free.3 Purification of the crude product by silica gel
chromatography afforded 13 along with a mixture of 14
and 15. The latter product resulted from an intramolecular
2. Results and discussion
As previously described,2 prenylation of 2,4-dihydroxy-
acetophenone was achieved in Lewis acidic medium with
2-methylbut-3-en-2-ol as the alkylating agent (Scheme 1).
In these conditions, the two monoprenylated derivatives 1
and 2 and the bis-prenylated compound 3 were obtained in
9, 21, and 6% yield respectively (Table 1). The same
method applied to the 2,6-dihydroxyacetophenone
furnished 4 and 5 in 42 and 11% yield, respectively. We
Keywords: Schenck ene reaction; prenyl chain; regioselectivity; large group
effect; phenolic assistance.
*
Corresponding author. Tel.: þ33-241-226-673; fax: þ33-241-486-733;
Scheme 1. Lewis acid mediated prenylation of phenolic derivatives. (i) 2-
methylbut-3-en-2-ol, BF3–Et2O, dioxane, rt.
e-mail: olivier.duval@univ-angers.fr
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00733-6

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Table 1. C-Prenylated derivatives produced via Scheme 1
Compound
R1
R2
R3
R4
Yield % (%a)
1
2
3
4
5
6
7
8
9
10
H
H
H
OH
H
OH
OH
H
H
H
H
H
COCH3
COCH3
COCH3
H
CH2–CHvC(CH3)2
CH3
Ph
COCH3
Br
Cl
OH
H
OH
H
H
H
H
H
H
H
9 (18)
21 (41)
5 (9)
42 (69)
11 (18)
31 (44)
22 (64)
8 (33)
CH2–CHvC(CH3)2
COCH3
COCH3
H
H
H
H
H
15 (26)
12 (32)
a
Yield based on recovered starting material.
Scheme 2. Photooxygenation–reduction sequence achieved at 2308C. (i) hn, O2, TPP, CH2Cl2, 2308C; (ii) PPh3, CH2Cl2, 2308C, 15 h; (iii) SiO2 (30%
AcOEt/cyclohexane).
cyclisation of the 3-hydroxy-3-methylbut-1-enyl side chain
with the unchelated phenolic group.
allylic hydroperoxide intermediate (HP-III, Scheme 3) and
1
was proved through H NMR analysis of the mixture of
allylic hydroperoxides 11 and 12, prepared at 2308C which
provided, after reduction, similar yields for the correspond-
ing alcohols 13 and 14 (Scheme 4a).1 The characteristic 1H
NMR signals for 12 rapidly disappeared when the
temperature was allowed to rise at 158C (Scheme 4b).
Photooxygenation–reduction sequence, achieved at 158C,
allowed us to isolate the secondary allylic alcohol as the sole
product in 66% yield (Scheme 3 and Table 2, entry 1). It is
known that tertiary allylic hydroperoxides could rearrange
into secondary corresponding hydroperoxides.4 In our case,
the selectivity was explained by the instability of the tertiary
Thus, by running the two-step sequence at 158C, several
Scheme 3. Photooxygenation–reduction sequence achieved at 158C. (i) hn, O2, TPP, CH2Cl2, 158C; (ii) PPh3, CH2Cl2, 158C, 15 h.

J.-J. Helesbeux et al. / Tetrahedron 59 (2003) 5091–5104
Table 2. Synthesis of secondary allylic alcohol via Scheme 3
5093
Entry
Starting material
R1
R2
R3
R4
Secondary allylic alcohol
Yield %
1
2
3
4
5
6
7
8
9
1
2
3
4
6
7
8
9
10
H
H
H
OH
H
OH
H
H
H
H
H
COCH3
COCH3
COCH3
H
CH3
Ph
COCH3
Br
Cl
OH
H
OH
H
H
H
H
H
H
13
16
17
18
20
21
23
24
25
66
84
56
65a
43
56b
58
44
51
CH2–CH(OH)–C(CH3)vCH2
COCH3
H
H
H
H
H
a
Accompanied by 3-acetyl-2,4-dihydroxybenzaldehyde 19 in 16% yield.
Accompanied by 2-(3-hydroxy-3-methylbut-1-enyl)-4-phenylphenol 22 in 32% yield.
b
secondary allylic alcohols were obtained with yields
ranging from 43 to 84% (Table 2). In most cases,
intermediate tertiary allylic hydroperoxide (HP-III,
Scheme 3) afforded spontaneously many degradation
products in such low quantity that they could not be
characterized. Nevertheless, isolation of by-products was
possible in two different experiments. Indeed, 3-acetyl-2,4-
dihydroxybenzaldehyde 19 was isolated, along with 18,
from 4 in 16% yield. 19, which was detectable by 1H NMR
analysis after the photooxidation step, could result from
the decomposition of an intermediate dioxetane, obtained
from a [2þ2] addition of singlet oxygen on the tertiary
allylic hydroperoxide double bond (Scheme 5).5 2-(3-
hydroxy-3-methylbut-1-enyl)-4-phenylphenol 22 was
obtained from 7 at 158C in 32% yield, along with 21
(Scheme 6). This unexpected result could be explained by a
greater stability of the corresponding hydroperoxide at this
temperature.
Scheme 4. 270 MHz 1H NMR spectra (CDCl3) of the photoxygenation reaction conducted at 08C (a) and at room temperature (b) from 1.

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J.-J. Helesbeux et al. / Tetrahedron 59 (2003) 5091–5104
Scheme 5. Formation of 19 during the photooxygenation step.
In the past, a great deal of work has been focused on the
regiochemical character of the singlet oxygen ene reaction.
These studies led to the definition of various effects that
could dictate the oxidation products distribution. Among
them and regarding ortho-prenylphenol structure, only the
cis effect and the large group non-bonded effect could be
involved in the distribution of our allylic hydroperoxides.6
As previously described for the photooxidation of 3-methyl-
but-2-enylbenzene,7 tertiary allylic hydroperoxides were
expected as major products. In our case, the main products
in the photooxygenation–reduction sequence were the
ortho-(2-hydroxy-3-methylbut-3-enyl)phenol derivatives.
Therefore, these results outlined a significant difference
with the empirical rule of the large group non-bonded effect,
phenyl substituents being probably responsible of such
regioselectivity. A similar modification of the oxidation
products distribution was already observed in the reaction of
1O2 with geminal dimethyl trisubstituted homoallylic
alcohols.6 Then, an assistance of the hydroxyl group was
postulated to explain such unusual regioselectivity. There-
fore, in our case, we suspected that the ortho-phenolic group
could be involved in the same type of stabilizing interaction
with the perepoxide intermediate. To confirm this
hypothesis, different derivatives related to 4 were prepared
and submitted to the photooxidation–reduction sequence
(Schemes 7 and 8). Then, we analysed and discussed the
ratio of secondary and tertiary allylic alcohols (ratio II/III,
Table 3).
Since the reduction step was considered as a quantitative
reaction, the ratio II/III of allylic alcohols was exactly
identical to the ratio of the corresponding hydroperoxides.
Compared to the previous results reported in Table 2,
formation of the alcohol 27a in a 30% yield at 158C (entry 1,
Table 3) pointed out the greater stability of the tertiary
allylic hydroperoxide when the phenolic group, para to the
prenyl side chain, was protected. Moreover, the first three
experiments (entry 1–3, Table 3) revealed that neither the
temperature of reaction nor the nature of the protective
group significantly affected the value of the ratio II/III. As
the dihydroxyacetophenone 4 furnished the alcohol 18 in
65% yield (entry 4, Table 2), the value of the ratio II/III
obtained from 4a and 4b (entry 2,3, Table 3) demonstrated
that protection of the phenolic group, para to the prenyl
appendage, disfavoured the formation of the secondary
allylic hydroperoxide. On an other hand, with the
protection of the phenolic group, ortho to the prenyl chain
Scheme 6. Reagents and conditions: (i) hn, O2, TPP, CH2Cl2, 158C; (ii) PPh3, CH2Cl2, 158C, 15 h.
Table 3. Ratio of secondary and tertiary allylic alcohols in the photooxygenation–reduction sequence of 4a–f
Entry
Starting material
R1
R2
Yields (%)
Secondary allylic alcohol 26a–f (II)
Ratio II/III
Tertiary allylic alcohol 27a–f (III)
1
2
3
4
5
6
7
4a
4a
4b
4c
4d
4e
4f
COCH3
COCH3
CH3
H
H
H
H
H
43
45
40
29
35
26
33
30
36
34
41
51
45
55
59/41a
55/45b
54/46b
41/59b
41/59b
34/66a
37/63a
CH3
CH2Ph
COCH3
CH3
COCH3
CH3
a
Photooxygenation–reduction sequence achieved at 158C.
Photooxygenation–reduction sequence achieved at 2308C.
b

J.-J. Helesbeux et al. / Tetrahedron 59 (2003) 5091–5104
5095
Scheme 7. Reagents and conditions: (i) CH3COCl (1 equiv.), NEt3 (1 equiv.), CH2Cl2, rt; (ii) Me2SO4 (1 equiv.), K2CO3, acetone, reflux; (iii) C6H5CH2Br
(1.5 equiv.), (C4H9)4NþI2, K2CO3, acetone, reflux; (iv) NaHCO3, MeOH, H2O, rt; (v) CH3COCl (4 equiv.), NEt3 (4 equiv.), CH2Cl2, rt.
(entry 4,5, Table 3), formation of tertiary allylic hydro-
peroxides was more favoured. The same regioselectivity
trend was observed when both phenolic groups were
protected (entry 6,7, Table 3).
bilities for the stabilization of the perepoxide, which was
likely the most acceptable intermediate.8 In accordance with
the previously defined ‘cis effect’,6 the conformation A
(Scheme 9) implied the interaction of the negatively
charged oxygen of the perepoxide with two allylic
hydrogens, in a perpendicular alignment to the double
bond plane. Thereby regarding this conformation, a mixture
of tertiary and secondary hydroperoxides was obtained. Due
to the well known large group non-bonded effect,6 allylic
hydrogens next to the phenyl group were more reactive. As
a consequence, transition state A led to the tertiary allylic
hydroperoxide as the major photooxidation product.
Following these experimental results, it was obvious that
evolution of the ratio II/III in favour of tertiary allylic
alcohols could be associated with the chemical modification
of the phenolic group, ortho to the prenyl side chain.
Photooxidation of a prenylated dihydroxyacetophenone led
predominantly to the secondary allylic hydroperoxide
derivative. Furthermore, with the protection of the ortho-
phenolic function (R2–H, Scheme 8), hydrogen abstraction
from the methylene group, leading to tertiary allylic
hydroperoxides, was more favoured than abstraction from
the methyl groups. To explain such observations, we
envisaged a competition between two coexistent possi-
In the conformation B (Scheme 10), stabilization of the
perepoxide intermediate no longer involved two allylic
hydrogens. Thus, hydrogen bonding between the negatively
charged oxygen and the phenolic function, ortho to the
Scheme 8. Reagents and conditions: (i) hn, O2, TPP, CH2Cl2; (ii) PPh3, CH2Cl2, 15 h.

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J.-J. Helesbeux et al. / Tetrahedron 59 (2003) 5091–5104
Scheme 9. Classical stabilization of the perepoxide intermediate.
Scheme 10. Stabilizing interaction hypothesis involving the perepoxide intermediate and the nearby phenolic hydrogen.
prenyl side chain, is proposed instead of an interaction with
the methylene hydrogens. Hence, transition state B could
only afford the secondary allylic hydroperoxide.
methyl groups were more reactive than allylic hydrogens
next to the phenyl ring. For the mechanistic interpretation of
these experimental results, we could envisage a stabilizing
interaction of the negatively charged oxygen of the
perepoxide intermediate with the phenolic hydrogen, ortho
to the prenyl side chain. Such effect was previously
demonstrated with hydroxyl groups in the photooxygena-
tion of homoallylic and allylic alcohols.6,9 Therefore, we
believe that in the series of substrates examined here, both
the classical large group effect and the phenolic hydrogen
assistance dictated the ene products distribution. As many
natural products isolated in our laboratory were substituted
by a 2-hydroxy-3-methylbut-3-enyl appendage, ortho to a
phenolic function, application of the photooxygenation–
reduction sequence to their synthesis will be reported in a
forthcoming paper.
Both phenols of the dihydroxyacetophenone 4 interacted
with the nearby ketone through hydrogen bonding. There-
fore, because of the protection of the phenolic group, para to
the prenyl side chain, the remaining phenol of 4a and 4b was
involved in a stronger chelation. As a consequence, the
phenolic hydrogen was less available to interact with the
negatively charged oxygen of the perepoxide intermediate.
In that case, transition state A was more favoured than
transition state B, leading to a noticeable decreased
percentage of secondary allylic alcohols in the ratio II/III
(entry 2,3, Table 3), compared to the 65% yield for 18
obtained from dihydroxyacetophenone 4 (entry 4, Table 2).
3. Conclusion
4. Experimental
4.1. General
In conclusion, in the present study, we reported a
straightforward access to ortho-(2-hydroxy-3-methylbut-3-
enyl)phenol derivatives from ortho-prenylphenol precursors
based on the Schenck reaction. We demonstrated that
achieving the photooxydation–reduction sequence at 158C
afforded solely the secondary allylic alcohol. As the tertiary
allylic hydroperoxide was the minor oxidation product, our
work also pointed out an original regioselectivity in the ene
reaction of singlet oxygen with ortho-prenylphenol com-
pounds. Hence, contrary to a reaction exclusively controled
by the large group non-bonded effect, allylic hydrogens of
Dioxane was distilled from sodium, using benzophenone as
indicator, dichloromethane was distilled from calcium
hydride. Si gel 60 (Macherey–Nagel, 230–400 mesh) was
used for column chromatography and precoated Si gel plates
(Macherey–Nagel, SIL G/UV254, 0.25 mm) were used for
preparative TLC. NMR spectra were recorded in CDCl3 or
CD3OD solutions on Bruker Avance DRX 500 and Jeol
GSX 270 WB instruments. IR spectra were recorded on a
Bruker Vector 22 spectrophotometer. HREIMS (70 eV) and

J.-J. Helesbeux et al. / Tetrahedron 59 (2003) 5091–5104
5097
HRFABMS were recorded on a Jeol JMS-700 spectrometer.
Melting points were determined on an Electrothermal 8100
melting point apparatus and are uncorrected.
cyclohexane) yielded 3 as a white powder (434 mg, 5%),
1
mp: 99–1008C; IR (cm21): 3299, 1630, 1583, 1207; H
NMR (CDCl3, 270 MHz): d 12.94 (s, 1H, OH), 7.36 (s, 1H
arom.), 6.23 (s, 1H, OH), 5.29 (t, 1H, CH2CH, J¼7 Hz),
5.25 (t, 1H, CH2CH, J¼7 Hz), 3.41 (d, 2H, CH2CH,
J¼7 Hz), 3.29 (d, 2H, CH2CH, J¼7 Hz), 2.55 (s, COCH3),
1.83 (s, 3H, CH3), 1.79 (s, 3H, CH3), 1.77 (s, 3H, CH3), 1.76
(s, 3H, CH3); 13C NMR (CDCl3, 67.5 MHz): d 202.7
(CvO), 161.0, 160.0 (2£quat. arom. C), 135.1, 134.5
(2£CHvC(CH3)2), 129.5 (arom. CH), 121.7, 121.3
(2£CH2CH), 118.8, 114.1, 113.4 (3£quat. arom. C), 29.0
(CH2CH), 26.2 (COCH3), 25.8 (2£CH3), 21.8 (CH2CH),
17.9 (2£CH3); EI-HRMS Calcd for C18H24O3 (Mþ)
288.1725, Found 288.1716.
4.2. General procedure for the preparation of prenylated
phenolic compounds
To a dioxane solution (8 ml/g) of phenolic derivative,
purchased commercially, was added 0.3 equiv. of boron
trifluoride etherate. Then, a dioxane solution of 2-methyl-
but-3-en-2-ol (1.2 equiv.) was poured dropwise over a
period of 50 min. The mixture was stirred at room
temperature for several days. Then an aqueous solution
(15%, 20 ml) of sodium acetate was added and the reaction
mixture was concentrated for elimination of dioxane. 50 ml
of ethyl acetate was added and the organic phase was
washed four times with a sodium acetate solution in water
(15%) (50 ml), dried over sodium sulfate and filtered. A
viscous crude oil was obtained after solvent elimination.
The mixture was then separated using liquid
chromatography.
4.2.4. 1-[2,6-Dihydroxy-3-(3-methylbut-2-enyl)phenyl]-
ethanone 4. The typical conditions described in Section
4.2 were employed with 2,6-dihydroxyacetophenone (3 g,
19.7 mmol). After 2 days, purification of the crude product
by column chromatography (15% AcOEt/cyclohexane)
yielded 4 as a yellow powder (1.82 g, 42%), mp: 80–
818C; IR (cm21): 3347, 1616, 1597, 1257; 1H NMR (CDCl3,
270 MHz): d 9.87 (br s, 1H, OH), 9.24 (br s, 1H, OH), 7.13
(d, 1H arom., J¼8 Hz), 6.33 (d, 1H arom., J¼8 Hz), 5.29 (t,
1H, CH2CH, J¼7.5 Hz), 3.29 (d, 2H, CH2CH, J¼7.5 Hz),
2.73 (s, 3H, COCH3), 1.78 (s, 6H, 2£CH3); 13C NMR
(CDCl3, 67.5 MHz): d 205.3 (CvO), 159.6, 159.4 (2£quat.
arom. C), 136.2 (arom. CH), 135.1 (CHvC(CH3)2), 121.6
(CH2CH), 119.2, 110.2 (2£quat. arom. C), 107.4 (arom.
CH), 33.6 (COCH3), 28.8 (CH2CH), 25.8 (CH3), 17.8
(CH3); EI-HRMS Calcd for C13H16O3 (Mþ) 220.1099,
Found 220.1102.
4.2.1. 1-[2,4-Dihydroxy-3-(3-methylbut-2-enyl)phenyl]-
ethanone 1. The typical conditions described in Section
4.2 were employed with 2,4-dihydroxyacetophenone (5 g,
32.9 mmol). After 2 days, purification of the crude product
by column chromatography (15% AcOEt/cyclohexane)
yielded 1 as a white powder (651 mg, 9%), mp: 128–
1308C; IR (cm21): 3170, 1623, 1589, 1273; 1H NMR
(CDCl3, 270 MHz): d 13.10 (s, 1H, OH), 7.55 (d, 1H arom.,
J¼8.5 Hz), 6.39 (d, 1H arom., J¼8.5 Hz), 6.12 (s, 1H, OH),
5.27 (t, 1H, CH2CH, J¼7 Hz), 3.45 (d, 2H, CH2CH,
J¼7 Hz), 2.57 (s, 3H, COCH3), 1.84 (s, 3H, CH3), 1.77 (s,
3H, CH3); 13C NMR (CDCl3, 67.5 MHz): d 202.8 (CvO),
162.5, 161.5 (2£quat. arom. C), 135.9 (CHvC(CH3)2),
130.3 (arom. CH), 121.0 (CH2CH), 113.8 (2£quat. arom.
C), 107.8 (arom. CH), 26.2 (COCH3), 25.8 (CH3), 21.6
(CH2CH), 17.9 (CH3); EI-HRMS Calcd for C13H16O3 (Mþ)
220.1099, Found 220.1102.
4.2.5. 1-[2,6-Dihydroxy-3,5-bis(3-methylbut-2-enyl)-
phenyl]ethanone 5. The typical conditions described in
Section 4.2 were employed with 2,6-dihydroxyaceto-
phenone (3 g, 19.7 mmol). After 2 days, purification of the
crude product by column chromatography (15% AcOEt/
cyclohexane) yielded 5 as a yellow oil (625 mg, 11%), IR
(cm21): 3418, 1618, 1228, 1090; 1H NMR (CDCl3,
270 MHz): d 9.64 (br s, 2H, OH), 7.01 (s, 2H arom.), 5.29
(t, 2H, 2£CH2CH, J¼7 Hz), 3.28 (d, 4H, 2£CH2CH,
4.2.2. 1-[2,4-Dihydroxy-5-(3-methylbut-2-enyl)phenyl]-
ethanone 2. The typical conditions described in Section
4.2 were employed with 2,4-dihydroxyacetophenone (5 g,
32.9 mmol). After 2 days, purification of the crude product
by column chromatography (15% AcOEt/cyclohexane)
yielded 2 as a white powder (1.52 g, 21%), mp: 124–
J¼7 Hz), 2.72 (s, 3H, COCH3), 1.78 (s, 12H, 4£CH3); 13
C
NMR (CDCl3, 67.5 MHz): d 205.5 (CvO), 157.7 (2£quat.
arom. C), 136.7 (arom. CH), 134.8 (2£CHvC(CH3)2),
121.9 (2£CH2CH), 118.2, 110.4 (3£quat. arom. C), 33.7
(COCH3), 28.8 (2£CH2CH), 25.8 (2£CH3), 17.8 (2£CH3);
EI-HRMS Calcd for C18H24O3 (Mþ) 288.1725, Found
288.1730.
1
1258C; IR (cm21): 3285, 1637, 1235; H NMR (CDCl3,
270 MHz): d 12.53 (s, 1H, OH), 9.41 (s, 1H, OH), 7.45 (s,
1H arom.), 6.37 (s, 1H arom.), 5.30 (t, 1H, CH2CH,
J¼7 Hz), 3.31 (d, 2H, CH2CH, J¼7 Hz), 2.57 (s, 3H,
COCH3), 1.80 (s, 6H, 2£CH3); 13C NMR (CDCl3,
67.5 MHz): d 202.8 (CvO), 163.7, 161.7 (2£quat. arom.
C), 135.6 (CHvC(CH3)2), 132.3 (arom. CH), 121.4
(CH2CH), 118.8, 114.2 (2£quat. arom. C), 103.8 (arom.
CH), 29.1 (CH2CH), 26.1 (COCH3), 25.7 (CH3), 17.8
(CH3); EI-HRMS Calcd for C13H16O3 (Mþ) 220.1099,
Found 220.1101.
4.2.6. 4-Methyl-2-(3-methylbut-2-enyl)phenol 6. The
typical conditions described in Section 4.2 were employed
with para-methylphenol (0.5 g, 4.6 mmol). After 4 days,
purification of the crude product by column chromato-
graphy (CH2Cl2) yielded 6 as a orange oil (253 mg, 31%),
IR (cm21): 3375, 1494, 1248; 1H NMR (CDCl3, 270 MHz):
d 6.89–6.95 (m, 2H arom.), 6.72 (d, 1H arom., J¼9 Hz),
5.33 (t, 1H, CH2CH, J¼7 Hz), 5.03 (s, 1H, OH), 3.34 (d, 2H,
CH2CH, J¼7 Hz), 2.28 (s, p-CH3), 1.80 (s, 3H, CH3), 1.79
(s, 3H, CH3); 13C NMR (CDCl3, 67.5 MHz): d 151.9 (quat.
arom. C), 134.3 (CHvC(CH3)2), 130.5 (arom. CH), 129.8
(quat. arom. C), 127.8 (arom. CH), 126.6 (quat. arom. C),
121.9 (CH2CH), 115.4 (arom. CH), 29.7 (CH2CH), 25.8
4.2.3. 1-[2,4-Dihydroxy-3,5-bis-(3-methylbut-2-enyl)-
phenyl]ethanone 3. The typical conditions described in
Section 4.2 were employed with 2,4-dihydroxyaceto-
phenone (5 g, 32.9 mmol). After 2 days, purification of the
crude product by column chromatography (15% AcOEt/

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(CH3), 20.5 (p-CH3), 17.8 (CH3); EI-HRMS Calcd for
C12H16O (Mþ) 176.1201, Found 176.1210.
5.33 (t, 1H, CH2CH, J¼7.5 Hz), 3.41 (d, 2H, CH2CH,
J¼7.5 Hz), 2.57 (s, 3H, COCH3), 1.79 (s, 3H, CH3), 1.78 (s,
3H, CH3); 13C NMR (CDCl3, 67.5 MHz): d 198.1 (CvO),
159.4 (quat. arom. C), 134.9 (CHvC(CH3)2), 130.8 (arom.
CH), 129.8 (quat. arom. C), 128.9 (arom. CH), 127.4 (quat.
arom. C), 121.2 (CH2CH), 115.4 (arom. CH), 29.3
(CH2CH), 26.3 (COCH3), 25.8 (CH3), 17.9 (CH3); EI-
HRMS Calcd for C13H16O2 (Mþ) 204.1150, Found
204.1150.
4.2.7. 2-(3-Methylbut-2-enyl)-4-phenylphenol 7. The
typical conditions described in Section 4.2 were employed
with para-phenylphenol (1 g, 5.9 mmol). After 3 days,
purification of the crude product by column chromato-
graphy (10% AcOEt/cyclohexane) yielded 7 as a colorless
oil (308 mg, 22%), IR (cm21): 3443, 1486; 1H NMR
(CDCl3, 270 MHz): d 7.56 (d, 2H arom., J¼9 Hz), 7.30–
7.45 (m, 5H arom.), 6.88 (d, 1H arom., J¼9 Hz), 5.38 (t, 1H,
CH2CH, J¼7 Hz), 5.19 (s, 1H, OH), 3.43 (d, 2H, CH2CH,
J¼7 Hz), 1.82 (s, 3H, CH3), 1.80 (s, 3H, CH3); 13C NMR
(CDCl3, 67.5 MHz): d 155.3, 141.0 (2£quat. arom. C),
135.0 (CHvC(CH3)2), 133.9 (quat. arom. C), 128.8, 128.6,
126.7, 126.6, 126.2 (7£arom. CH), 125.8 (quat. arom. C),
121.6 (CH2CH), 116.0 (arom. CH), 30.0 (CH2CH), 25.8
(CH3), 17.9 (CH3); EI-HRMS Calcd for C17H18O (Mþ)
238.1358, Found 238.1358.
4.2.11. 1-[4-(3-Methylbut-2-enyloxy)phenyl]ethanone 8a.
The typical conditions described in Section 4.2 were
employed with 4-hydroxyacetophenone (0.5 g, 3.7 mmol).
After 2 days, purification of the crude product by column
chromatography (30% AcOEt/cyclohexane) yielded 8a as a
colorless oil (44 mg, 6%), IR (cm21): 1675, 1598, 1244; 1H
NMR (CDCl3, 270 MHz): d 7.93 (d, 2H arom., J¼9 Hz),
6.93 (d, 2H arom., J¼9 Hz), 5.49 (t, 1H, CH2CH, J¼7 Hz),
4.57 (d, 2H, CH2CH, J¼7 Hz), 2.56 (s, 3H, COCH3), 1.80
(s, 3H, CH3), 1.76 (s, 3H, CH3); 13C NMR (CDCl3,
67.5 MHz): d 196.8 (CvO), 162.8 (quat. arom. C), 138.6
(CHvC(CH3)2), 130.5 (arom. CH), 130.1 (quat. arom. C),
118.9 (CH2CH), 114.3 (arom. CH), 64.9 (CH2CH), 26.3
(COCH3), 25.8 (CH3), 18.2 (CH3); EI-HRMS Calcd for
C13H16O2 (Mþ) 204.1150, Found 204.115.
4.2.8. 4-[(3-Methylbut-2-enyl)oxy]-1,10-biphenyl 7a. The
typical conditions described in Section 4.2 were employed
with para-phenylphenol (1 g, 5.9 mmol). After 3 days,
purification of the crude product by column chromato-
graphy (10% AcOEt/cyclohexane) yielded 7a as a white
solid (120 mg, 9%), mp: 59–618C; IR (cm21): 1607, 1488,
1
1270; H NMR (CDCl3, 270 MHz): d 7.59–7.51 (m, 4H
4.2.12. 4-Bromo-2-(3-methylbut-2-enyl)phenol 9. The
typical conditions described in Section 4.2 were employed
with para-bromophenol (5 g, 17.3 mmol). After 3 days,
purification of the crude product by column chromato-
graphy (35% AcOEt/cyclohexane) yielded 9 as a orange oil
arom.), 7.45–7.40 (m, 5H arom.), 7.34–7.28 (m, 1H arom.),
7.01 (d, 2H arom., J¼9 Hz), 5.55 (t, 1H, CH2CH, J¼7 Hz),
4.57 (d, 2H, CH2CH, J¼7 Hz), 1.84 (s, 3H, CH3), 1.79 (s,
3H, CH3); 13C NMR (CDCl3, 67.5 MHz): d 158.3, 140.7
(quat. arom. C), 138.2 (CHvC(CH3)2), 133.6 (quat. arom.
C), 128.6, 128.0, 126.6, 126.5 (7£arom. CH), 119.6
(CH2CH), 114.8 (arom. CH), 64.8 (CH2CH), 25.9 (CH3),
18.3 (CH3); EI-HRMS Calcd for C17H18O (Mþ) 238.1358,
Found 238.1360.
1
(626 mg, 15%), IR (cm21): 3416, 1481, 1266; H NMR
(CDCl3, 270 MHz): d 7.22 (s, 1H arom.), 7.20 (d, 1H arom.,
J¼7 Hz), 6.69 (d, 1H arom., J¼7 Hz), 5.33 (t, 1H, CH2CH,
J¼7 Hz), 5.25 (s, 1H, OH), 3.37 (d, 2H, CH2CH, J¼7 Hz),
1.84 (s, 3H, CH3), 1.82 (s, 3H, CH3); 13C NMR (CDCl3,
67.5 MHz): d 153.4 (quat. arom. C), 135.6 (CHvC(CH3)2),
132.4, 130.1 (arom. CH), 129.2 (quat. arom. C), 120.8
(CH2CH), 117.3 (arom. CH), 112.6 (quat. arom. C), 29.4
(CH2CH), 25.8 (CH34), 17.9 (CH3); EI-HRMS Calcd for
C11H13BrO (Mþ) 240.0150, Found 240.0145.
4.2.9. 3,5-Bis(3-methylbut-2-enyl)-4-phenylphenol 7b.
The typical conditions described in Section 4.2 were
employed with para-phenylphenol (1 g, 5.9 mmol). After
3 days, purification of the crude product by column
chromatography (10% AcOEt/cyclohexane) yielded 7b as
a colorless oil (54 mg, 3%), IR (cm21): 3459, 1469, 1183;
1H NMR (CDCl3, 270 MHz): d 7.57–7.52 (m, 2H arom.),
7.45–7.38 (m, 2H arom.), 7.33–7.28 (m, 1H arom.), 7.23 (s,
2H arom.), 5.44 (s, 1H, OH), 5.38 (t, 1H, CH2CH,
J¼7.5 Hz), 3.43 (d, 2H, CH2CH, J¼7.5 Hz), 1.82 (s, 3H,
CH3), 1.80 (s, 3H, CH3); 13C NMR (CDCl3, 67.5 MHz): d
152.2, 141.2 (quat. arom. C), 134.3 (2£CHvC(CH3)2),
133.4 (quat. arom. C), 128.5, 127.4, 126.8, 126.6 (7£arom.
CH), 122.0 (2£CH2CH), 29.9 (2£CH2CH), 25.9 (2£CH3),
18.0 (2£CH3); EI-HRMS Calcd for C22H26O (Mþ)
306.1984, Found 305.1543.
4.2.13. 1-Bromo-4-[(3-methylbut-2-enyl)oxy]benzene 9a.
The typical conditions described in Section 4.2 were
employed with para-bromophenol (5 g, 17.3 mmol). After
3 days, purification of the crude product by column
chromatography (35% AcOEt/cyclohexane) yielded 9a as
1
an orange oil (334 mg, 8%), IR (cm21): 1486, 1234; H
NMR (CDCl3, 270 MHz): d 7.37 (d, 2H arom., J¼9 Hz),
6.80 (d, 2H arom., J¼9 Hz), 5.47 (t, 1H, CH2CH, J¼7 Hz),
4.48 (d, 2H, CH2CH, J¼7 Hz), 1.80 (s, 3H, CH3), 1.75 (s,
3H, CH3); 13C NMR (CDCl3, 67.5 MHz): d 157.9 (quat.
arom. C), 138.6 (CHvC(CH3)2), 132.2 (arom. CH), 119.2
(CH2CH), 116.5 (arom. CH), 112.7 (quat. arom. C), 65.0
(CH2CH), 25.8 (CH34), 18.2 (CH3).
4.2.10. 1-[4-Hydroxy-3-(3-methylbut-2-enyl)phenyl]-
ethanone 8. The typical conditions described in Section
4.2 were employed with 4-hydroxyacetophenone (0.5 g,
3.7 mmol). After 2 days, purification of the crude product by
column chromatography (30% AcOEt/cyclohexane) yielded
8 as a white powder (60 mg, 8%), mp: 66–688C; IR (cm21):
4.2.14. 4-Chloro-2-(3-methylbut-2-enyl)phenol 10. The
typical conditions described in Section 4.2 were employed
with para-chlorophenol (5 g, 38.9 mmol). After 3 days,
purification of the crude product by column chromato-
graphy (35% AcOEt/cyclohexane) yielded 10 as a orange
oil (930 mg, 12%), IR (cm21): 3401, 1482, 1264; 1H NMR
(CDCl3, 270 MHz): d 7.20 (d, 1H arom., J¼2.5 Hz), 7.14
1
3239, 1653, 1587, 1276; H NMR (CDCl3, 270 MHz): d
7.78 (dd, 1H arom., J¼8 Hz, 2.5 Hz), 7.75 (d, 1H arom.,
J¼2.5 Hz), 6.88 (d, 1H arom., J¼8 Hz), 6.70 (s, 1H, OH),

J.-J. Helesbeux et al. / Tetrahedron 59 (2003) 5091–5104
5099
(dd, 1H arom., J¼8.5 Hz, 2.5 Hz), 6.64 (dd, 1H arom.,
J¼8.5 Hz, 2.5 Hz), 5.27 (t, 1H, CH2CH, J¼7 Hz), 5.13 (s,
1H, OH), 3.29 (d, 2H, CH2CH, J¼7 Hz), 1.76 (s, 3H, CH3),
1.72 (s, 3H, CH3); 13C NMR (CDCl3, 67.5 MHz): d 152.9
(quat. arom. C), 135.6 (CHvC(CH3)2), 129.6 (arom. CH),
128.6 (quat. arom. C), 127.2 (arom. CH), 125.3 (quat. arom.
C), 120.8 (CH2CH), 116.8 (arom. CH), 29.5 (CH2CH), 25.8
(CH3), 17.9 (CH3); EI-HRMS Calcd for C11H13ClO (Mþ)
196.0655, Found 196.0647.
4.38 (dd, 1H, CH2CHOH, J¼8 Hz, 2 Hz), 3.15 (dd, 1H,
CH2CHOH, J¼15 Hz, 2 Hz), 2.85 (dd, 1H, CH2CHOH,
J¼15 Hz, 8 Hz), 2.55 (s, 3H, COCH3), 1.85 (s, 3H, CH3);
13C NMR (CDCl3, 67.5 MHz): d 202.8 (CvO), 163.3,
163.0 (2£quat. arom. C), 146.7 (CH2vC(CH3)), 130.9
(arom. CH), 113.4, 112.8 (2£quat. arom. C), 110.4 (CH2-
vC(CH3)), 109.0 (arom. CH), 77.5 (CH2CHOH), 28.3
(CH2CHOH), 26.2 (COCH3), 18.5 (CH3); FAB-HRMS
Calcd for C13H17O4 ([MþH]þ) 237.1127, Found 237.1129.
4.2.15. 1-Chloro-4-[(3-methylbut-2-enyl)oxy]benzene
10a. The typical conditions described in Section 4.2 were
employed with para-chlorophenol (5 g, 38.9 mmol). After 3
days, purification of the crude product by column
chromatography (35% AcOEt/cyclohexane) yielded 10a as
4.4.2. 1-[2,4-Dihydroxy-5-(2-hydroxy-3-methylbut-3-
enyl)phenyl]ethanone 16. The typical conditions described
in Section 4.3 were employed with 2 (30 mg, 0.14 mmol).
The purification of the crude product according to procedure
A yielded 16 as a green oil (27 mg, 84%), IR (cm21): 3442,
1638, 1598, 1280; 1H NMR (CDCl3, 270 MHz): d 12.48 (s,
1H, OH), 9.41 (s, 1H, OH), 7.37 (s, 1H arom.), 6.41 (s, 1H
arom.), 5.01 (br s, 1H, CvCH2), 4.89 (br s, 1H, CvCH2),
4.38 (dd, 1H, CH2CHOH, J¼8.5 Hz, 2.5 Hz), 2.90 (dd, 1H,
CH2CHOH, J¼15 Hz, 2.5 Hz), 2.77 (dd, 1H, CH2CHOH,
J¼15 Hz, 8.5 Hz), 2.52 (s, 3H, COCH3), 1.80 (s, 3H, CH3);
13C NMR (CDCl3, 67.5 MHz): d 202.8 (CvO), 164.3,
163.6 (2£quat. arom. C), 146.0 (CH2vC(CH3)), 134.1
(arom. CH), 117.6, 113.5 (2£quat. arom. C), 111.7 (CH2-
vC(CH3)), 105.1 (arom. CH), 77.8 (CH2CHOH), 37.6
(CH2CHOH), 26.1 (COCH3), 18.0 (CH3); FAB-HRMS
Calcd for C13H17O4 ([MþH]þ) 237.1127, Found 237.1121.
1
a colorless oil (860 mg, 11%), IR (cm21): 1490, 1237; H
NMR (CDCl3, 270 MHz): d 7.28 (d, 2H arom., J¼9 Hz),
6.90 (d, 2H arom., J¼9 Hz), 5.53 (t, 1H, CH2CH, J¼7 Hz),
4.54 (d, 2H, CH2CH, J¼7 Hz), 1.85 (s, 3H, CH3), 1.80 (s,
3H, CH3); 13C NMR (CDCl3, 67.5 MHz): d 157.4 (quat.
arom. C), 137.9 (CHvC(CH3)2), 129.2 (arom. CH), 119.3
(CH2CH), 118.2 (quat. arom. C), 115.9 (arom. CH), 65.0
(CH2CH), 25.8 (CH3), 18.2 (CH3); EI-HRMS Calcd for
C11H13ClO (Mþ) 196.0655, Found 196.066.
4.3. General procedure for the photooxygenation–
reduction sequence at 158C
Dried air was bubbled through a CH2Cl2 solution (30 ml) of
phenolic prenylated compound (30 mg) and tetraphenyl-
porphine (3 mg, 0.005 mmol) as the photosensitizer. The
reaction mixture was water-cooled at 158C and irradiated
with a halogen lamp (500 W) for 1.5 h. Then 1.1 equiv. of
triphenylphosphine was added and the solution was stirred
overnight at room temperature.
4.4.3. 1-[2,4-Dihydroxy-3,5-bis-(2-hydroxy-3-methylbut-
3-enyl)phenyl]ethanone 17. The typical conditions
described in Section 4.3 were employed with 3 (30 mg,
0.10 mmol). The purification of the crude product according
to procedure A yielded 17 as an orange oil (19 mg, 56%), IR
1
(cm21): 3442, 1626, 1372; H NMR (CDCl3, 270 MHz): d
13.00 (s, 1H, OH), 9.80 (s, 1H, OH), 7.38 (s, 1H arom.), 5.00
(br s, 2H, CvCH2), 4.88 (br s, 1H, CvCH2), 4.85 (br s, 1H,
CvCH2), 4.30–4.35 (m, 2H, 2£CH2CHOH), 3.09–3.17
(m, 2H, CH2CHOH), 2.81–2.94 (m, 2H, CH2CHOH), 2.56
(s, 3H, COCH3), 1.85 (s, 3H, CH3), 1.82 (s, 3H, CH3); 13C
NMR (CDCl3, 67.5 MHz): d 202.7 (CvO), 161.9, 161.5
(2£quat. arom. C), 147.1, 146.7 (2£CH2vC(CH3)), 131.9
(arom. CH), 117.7, 113.7 (2£quat. arom. C), 111.1, 110.2
(2£CH2vC(CH3)), 76.6, 76.8 (2£CH2CHOH), 37.6 (2£
CH2CHOH), 29.0 (COCH3), 18.3, 18.1 (2£CH3); EI-HRMS
Calcd for C18H24O5 (Mþ) 320.1624, Found 320.1620.
4.4. Purification
Procedure A. The reaction mixture was washed four times
with 30 ml of an aqueous solution of potassium carbonate
(10%). The combined aqueous layers were acidified down to
pH¼3 by addition of water-diluted chlorhydric acid (10%).
Then this solution was extracted four times with 30 ml of
dichloromethane. The combined organic layers were
concentrated under reduced pressure and were subjected
to a second cycle of basic extraction. The final organic
layers were evaporated under reduced pressure and yielded
the purified secondary allylic alcohol derivative.
4.4.4. 1-[2,6-Dihydroxy-3-(2-hydroxy-3-methylbut-3-
enyl)phenyl]ethanone 18. The typical conditions described
in Section 4.3 were employed with 4 (30 mg, 0.14 mmol).
After purification of the crude product according to
procedure A, a preparative TLC of the oily residue followed
by a recristallization in AcOEt/hexane afforded 18 as yellow
cristals (21 mg, 65%), mp: 100–1018C; IR (cm21): 3223,
Procedure B. This procedure only differed from the
preceding procedure by the nature of the basic solution.
Here, we used an aqueous solution of potassium hydroxide
(5%).
1
1626, 1269; H NMR (CDCl3, 270 MHz): d 12.38 (s, 1H,
4.4.1. 1-[2,4-Dihydroxy-3-(2-hydroxy-3-methylbut-3-
enyl)phenyl]ethanone 13. The typical conditions described
in Section 4.3 were employed with 1 (30 mg, 0.14 mmol).
The purification of the crude product according to procedure
A followed by a recristallization in AcOEt/hexane afforded
13 as white cristals (21 mg, 66%), mp: 79–808C; IR (cm21):
3442, 1617, 1270; 1H NMR (CDCl3, 270 MHz): d 13.11 (s,
1H, OH), 7.55 (d, 1H arom., J¼9 Hz), 6.47 (d, 1H arom.,
J¼9 Hz), 4.99 (br s, 1H, CvCH2), 4.86 (br s, 1H, CvCH2),
OH), 9.88 (s, 1H, OH), 7.07 (d, 1H arom., J¼8.5 Hz), 6.40
(d, 1H arom., J¼8.5 Hz), 5.00 (br s, 1H, CvCH2), 4.90 (br
s, 1H, CvCH2), 4.39 (dd, 1H, CH2CHOH, J¼8.5 Hz,
3 Hz), 2.89 (dd, 1H, CH2CHOH, J¼15 Hz, 8.5 Hz), 2.76
(dd, 1H, CH2CHOH, J¼15 Hz, 3 Hz), 2.75 (s, 3H, COCH3),
1.81 (s, 3H, CH3); 13C NMR (CDCl3, 67.5 MHz): d
206.0 (CvO), 162.5, 159.1 (2£quat. arom. C), 146.1
(CH2vC(CH3)), 138.1 (arom. CH), 116.4, 111.5 (2£quat.
arom. C), 111.4 (CH2vC(CH3)), 108.6 (arom. CH), 78.2

5100
J.-J. Helesbeux et al. / Tetrahedron 59 (2003) 5091–5104
(CH2CHOH), 37.6 (CH2CHOH), 33.8 (COCH3), 18.2
(CH3); EI-HRMS Calcd for C13H16O4 (Mþ) 236.1048,
Found 236.1051.
mp: 156–1578C, IR (cm21): 3297, 1272; 1H NMR (CDCl3,
270 MHz): d 7.59 (d, 1H arom., J¼2 Hz), 7.53 (d, 2H arom.,
J¼8 Hz), 7.37 (dd, 2H arom., J¼8 Hz, 7.5 Hz), 7.29 (dd, 1H
arom., J¼8.5 Hz, 2 Hz), 7.24 (t, 1H arom., J¼7.5 Hz), 6.90
(d, 1H, CH¼CH, J¼16.5 Hz), 6.84 (d, 1H arom.,
J¼8.5 Hz), 6.44 (d, 1H, CH¼CH, J¼16.5 Hz), 1.40 (s,
6H, 2£CH3); EI-HRMS Calcd for C17H18O2 (Mþ)
254.1307, Found 254.1297.
4.4.5. 3-Acetyl-2,4-dihydroxybenzaldehyde 19. The typi-
cal conditions described in Section 4.3 were employed with
4 (30 mg, 0.14 mmol). After purification of the crude
product according to procedure A, a preparative TLC of the
oily residue afforded 19 as a colorless oil (4 mg, 16%), IR
1
(cm21): 1625, 1590, 1242; H NMR (CDCl3, 270 MHz): d
4.4.9. 1-[4-Hydroxy-3-(2-hydroxy-3-methylbut-3-enyl)-
phenyl]ethanone 23. The typical conditions described in
Section 4.3 were employed with 8 (30 mg, 0.15 mmol). The
purification of the crude product according to procedure B
yielded 23 as a white solid (19 mg, 58%), mp: 96–978C, IR
(cm21): 3368, 1662, 1587, 1281; 1H NMR (CDCl3,
270 MHz): d 9.21 (s, 1H, OH), 7.77 (dd, 1H arom.,
J¼8.5 Hz, 2.5 Hz), 7.71 (d, 1H arom., J¼2.5 Hz), 6.94 (d,
1H arom., J¼8.5 Hz), 5.01 (br s, 1H, CvCH2), 4.88 (br s,
1H, CvCH2), 4.43 (dd, 1H, CH2CHOH, J¼8.5 Hz, 2.5 Hz),
2.95 (dd, 1H, CH2CHOH, J¼14.5 Hz, 8.5 Hz), 2.73 (dd, 1H,
CH2CHOH, J¼14.5 Hz, 2.5 Hz), 2.54 (s, 3H, COCH3), 1.81
(s, 3H, CH3); 13C NMR (CDCl3, 67.5 MHz): d 197.5
(CvO), 160.8 (quat. arom. C), 146.1 (CH2vC(CH3)),
130.2, 129.9 (2£arom. CH), 129.7, 125.6 (2£quat. arom. C),
117.0 (arom. CH), 111.4 (CH2vC(CH3)), 77.7 (CH2-
CHOH), 38.2 (CH2CHOH), 26.3 (COCH3), 18.2 (CH3);
EI-HRMS Calcd for C13H16O3 (Mþ) 220.1099, Found
220.1103.
14.37 (s, 1H, OH), 13.42 (s, 1H, OH), 9.68 (s, 1H, CHO),
7.58 (d, 1H arom., J¼8.5 Hz), 6.58 (d, 1H arom.,
J¼8.5 Hz), 2.80 (s, 3H, COCH3); 13C NMR (CDCl3,
67.5 MHz): d 205.1 (COCH3), 194.5 (CHO), 171.4, 167.2
(2£quat. arom. C), 140.4 (arom. CH), 113.3 (quat. arom. C),
110.9 (arom. CH), 109.3 (quat. arom. C), 33.4 (COCH3);
EI-HRMS Calcd for C9H8O4 (Mþ) 180.0423, Found
180.0420.
4.4.6. 2-(2-Hydroxy-3-methylbut-3-enyl)-4-methyl-
phenol 20. The typical conditions described in Section 4.3
were employed with 6 (30 mg, 0.17 mmol). The purification
of the crude product according to procedure B yielded 20 as
a beige solid (14 mg, 43%), mp: 55–578C, IR (cm21): 3301,
1
1501, 1243; H NMR (CDCl3, 270 MHz): d 7.97 (s, 1H,
OH), 6.96 (dd, 1H arom., J¼8.5 Hz, 2 Hz), 6.86 (d, 1H
arom., J¼2 Hz), 6.82 (d, 1H arom., J¼8.5 Hz), 5.01 (br s,
1H, CvCH2), 4.89 (br s, 1H, CvCH2), 4.36 (dd, 1H,
CH2CHOH, J¼9 Hz, 2 Hz), 2.95 (dd, 1H, CH2CHOH,
J¼14.5 Hz, 9 Hz), 2.73 (dd, 1H, CH2CHOH, J¼14.5 Hz,
2 Hz), 2.26 (s, 3H, p-CH3), 1.83 (s, 3H, CH3); 13C NMR
(CDCl3, 67.5 MHz): d 153.2 (quat. arom. C), 146.1
(CH2vC(CH3)), 131.8 (arom. CH), 129.5 (quat. arom. C),
128.8 (arom. CH), 125.4 (quat. arom. C), 117.0 (arom. CH),
111.1 (CH2vC(CH3)), 78.4 (CH2CHOH), 38.0 (CH2-
CHOH), 20.4 (p-CH3), 18.1 (CH3); FAB-HRMS Calcd for
C12H16O2 (Mþ) 192.1150, Found 192.1155.
4.4.10. 2-(2-Hydroxy-3-methylbut-3-enyl)-4-bromo-phe-
nol 24. The typical conditions described in Section 4.3 were
employed with 9 (30 mg, 0.12 mmol). The purification of
the crude product according to procedure B yielded 24 as a
colorless oil (14 mg, 44%), IR (cm21): 3287, 1481, 1239;
1H NMR (CDCl3, 270 MHz): d 8.26 (s, 1H, OH), 7.24 (dd,
1H arom., J¼8.5 Hz, 2.5 Hz), 7.15 (d, 1H arom., J¼2.5 Hz),
6.81 (d, 1H arom., J¼8.5 Hz), 5.01 (br s, 1H, CvCH2),
4.91 (br s, 1H, CvCH2), 4.40 (dd, 1H, CH2CHOH,
J¼8.5 Hz, 2 Hz), 2.94 (dd, 1H, CH2CHOH, J¼15 Hz,
8.5 Hz), 2.74 (dd, 1H, CH2CHOH, J¼15 Hz, 2 Hz), 2.54 (s,
1H, CH2CHOH), 1.82 (s, 3H, CH3); 13C NMR (CDCl3,
67.5 MHz): d 154.9 (quat. arom. C), 146.1 (CH2vC(CH3)),
133.6, 131.1 (2£arom. CH), 127.8 (quat. arom. C), 119.1
(arom. CH), 111.5 (CH2vC(CH3)), 112.0 (quat. arom. C),
78.1 (CH2CHOH), 37.7 (CH2CHOH), 18.1 (CH3);
EI-HRMS Calcd for C11H13BrO2 (Mþ) 256.0099, Found
256.0087.
4.4.7. 2-(2-Hydroxy-3-methylbut-3-enyl)-4-phenyl-
phenol 21. The typical conditions described in Section 4.3
were employed with 7 (30 mg, 0.13 mmol). Purification of
the crude product by preparative TLC (30% AcOEt/
cyclohexane) yielded 21 as a white solid (18 mg, 56%),
mp: 115–1168C, IR (cm21): 3229, 1281; 1H NMR (CDCl3,
270 MHz): d 7.55 (dd, 2H arom., J¼8 Hz, 1.5 Hz), 7.45–
7.39 (m, 3H arom.), 7.34–7.31 (m, 1H arom.), 7.29 (d, 1H
arom., J¼2.5 Hz), 7.01 (d, 1H arom., J¼8.5 Hz), 4.98 (br s,
1H, CvCH2), 4.85 (br s, 1H, CvCH2), 4.45 (dd, 1H,
CH2CHOH, J¼9 Hz, 2 Hz), 3.06 (dd, 1H, CH2CHOH,
J¼14.5 Hz, 9 Hz), 2.87 (dd, 1H, CH2CHOH, J¼14.5 Hz,
2 Hz), 1.86 (s, 3H, CH3); 13C NMR (CDCl3, 67.5 MHz): d
155.3 (quat. arom. C), 146.5 (CH2vC(CH3)), 140.9, 133.5
(2£quat. arom. C), 130.0, 128.6, 127.1, 126.7, 126.5
(7£arom. CH), 125.8 (quat. arom. C), 117.6 (arom. CH),
111.3 (CH2vC(CH3)), 78.4 (CH2CHOH), 38.2 (CH2-
CHOH), 18.2 (CH3); EI-HRMS Calcd for C17H18O2 (Mþ)
254.1307, Found 254.1294.
4.4.11. 2-(2-Hydroxy-3-methylbut-3-enyl)-4-chloro-phe-
nol 25. The typical conditions described in Section 4.3 were
employed with 10 (30 mg, 0.15 mmol). The purification of
the crude product according to procedure B yielded 25 as a
colorless oil (17 mg, 51%), IR (cm21): 3384, 1485, 1245;
1H NMR (CDCl3, 270 MHz): d 8.19 (s, 1H, OH), 7.11 (dd,
1H arom., J¼8.5 Hz, 2.5 Hz), 7.01 (d, 1H arom., J¼2.5 Hz),
6.85 (d, 1H arom., J¼8.5 Hz), 5.01 (br s, 1H, CvCH2), 4.91
(br s, 1H, CvCH2), 4.41 (dd, 1H, CH2CHOH, J¼9 Hz,
2.5 Hz), 2.95 (dd, 1H, CH2CHOH, J¼15 Hz, 9 Hz), 2.75
(dd, 1H, CH2CHOH, J¼15 Hz, 2.5 Hz), 2.49 (s, 1H,
CH2CHOH), 1.82 (s, 3H, CH3); 13C NMR (CDCl3,
67.5 MHz): d 154.4 (quat. arom. C), 146.1 (CH2vC(CH3)),
130.7, 128.1 (2£arom. CH), 127.2, 124.7 (2£quat.
arom. C), 118.6 (arom. CH), 111.4 (CH2vC(CH3)), 78.1
4.4.8. 2-(3-Hydroxy-3-methylbut-1-enyl)-4-phenyl-
phenol 22. The typical conditions described in Section 4.3
were employed with 7 (30 mg, 0.13 mmol). Purification of
the crude product by preparative TLC (30% AcOEt/
cyclohexane) yielded 22 as a yellow solid (10 mg, 32%),

J.-J. Helesbeux et al. / Tetrahedron 59 (2003) 5091–5104
5101
(CH2CHOH), 37.7 (CH2CHOH), 18.1 (CH3); EI-HRMS
Calcd for C11H13ClO2 (Mþ) 212.0604, Found 212.0604.
Na2SO4. Removal of the solvent under reduced pressure
yielded 4g as a colorless oil (128 mg, 97%), IR (cm21):
1772, 1700, 1199; H NMR (CDCl3, 270 MHz): d 7.22 (d,
1
4.4.12. 2-Acetyl-3-hydroxy-4-(3-methylbut-2-enyl)phe-
nyl acetate 4a. To a CH2Cl2 solution (30 ml) of
1H arom., J¼7.5 Hz), 6.82 (d, 1H arom., J¼7.5 Hz), 5.25 (t,
1H, CH2CH, J¼7.5 Hz), 3.72 (s, 3H, OCH3), 3.34 (d, 2H,
CH2CH, J¼7.5 Hz), 2.53 (s, 3H, COCH3), 2.23 (s, 3H,
OCOCH3), 1.75 (s, 3H, CH3), 1.72 (s, 3H, CH3); 13C NMR
(CDCl3, 67.5 MHz): d 201.1 (COCH3), 169.3 (OCOCH3),
155.5, 145.2 (2£quat. arom. C), 133.3 (CHvC(CH3)2),
132.9 (quat. arom. C), 131.4 (arom. CH), 128.8 (quat. arom.
C), 121.8 (CH2CH), 118.4 (arom. CH), 62.7 (OCH3), 31.5
(COCH3), 27.6 (CH2CH), 25.7 (CH3), 20.8 (OCOCH3),
17.8 (CH3); EI-MS m/z 276 (Mþ, 20), 234 (74), 220 (14),
219 (100), 177 (12), 43 (51).
dihydroxyacetophenone
4 (300 mg, 1.36 mmol) were
added triethylamine (0.19 ml, 1.36 mmol) and acetyl
chloride (97 ml, 1.36 mmol). The resulting solution was
strirred overnight at room temperature. Then the reaction
mixture was successively washed with 2£25 ml of water,
2£25 ml of diluted HCl and 2£25 ml of water. The organic
layer was dried over sodium sulfate, filtered and the solvent
was evaporated under reduced pressure. Purification of the
crude product by column chromatography (10% AcOEt/
cyclohexane) yielded 4a as an orange oil (304 mg, 85%), IR
(cm21): 3443, 1771, 1628, 1192; 1H NMR (CDCl3,
270 MHz): d 13.08 (s, 1H, OH), 7.31 (d, 1H arom.,
J¼7.5 Hz), 6.54 (d, 1H arom., J¼7.5 Hz), 5.30 (t, 1H,
CH2CH, J¼7.5 Hz), 3.33 (d, 2H, CH2CH, J¼7.5 Hz), 2.62
(s, 3H, COCH3), 2.37 (s, 3H, OCOCH3), 1.79 (s, 3H, CH3),
1.70 (s, 3H, CH3); 13C NMR (CDCl3, 67.5 MHz): d 203.3
(COCH3), 169.1 (OCOCH3), 161.7, 149.1 (2£quat. arom.
C), 134.9 (arom. CH), 133.7 (CHvC(CH3)2), 128.7 (quat.
arom. C), 121.2 (CH2CH), 113.6 (quat. arom. C), 113.1
(arom. CH), 32.2 (COCH3), 27.7 (CH2CH), 25.8 (CH3),
21.6 (OCOCH3), 17.8 (CH3); EI-HRMS Calcd for
C15H18O4 (Mþ) 262.1205, Found 262.1202.
4.4.15. 1-[6-Hydroxy-2-methoxy-3-(3-methylbut-2-enyl)-
phenyl]ethanone 4c. Monoacetate derivative 4g (72 mg,
0.26 mmol) was dissolved in a 2:1:1 ratio mixture (12 ml) of
methanol/aqueous saturated NaHCO3 solution/water.
This reaction mixture was stirred at room temperature
for 40 min. Then diluted HCl (10%) was added down to
pH¼2. The resulting mixture was extracted four times
with 15 ml of AcOEt. The combined organic layers were
washed with 2£25 ml of water and dried over Na2SO4.
Removal of the solvent under reduced pressure yielded,
without further purification, 4c as a colorless oil (59 mg,
70%), IR (cm21): 3448, 1632, 1468, 1219; 1H NMR
(CDCl3, 270 MHz): d 12.44 (s, 1H, OH), 7.28 (d, 1H arom.,
J¼9 Hz), 6.73 (d, 1H arom., J¼9 Hz), 5.24 (t, 1H, CH2CH,
J¼7.5 Hz), 3.76 (s, 3H, OCH3), 3.30 (d, 2H, CH2CH,
J¼7.5 Hz), 2.75 (s, 3H, COCH3), 1.76 (s, 3H, CH3), 1.741
(s, 3H, CH3); 13C NMR (CDCl3, 67.5 MHz): d 205.2
(CvO), 161.7, 159.4 (2£quat. arom. C), 137.4 (arom. CH),
133.1 (CHvC(CH3)2), 125.3 (quat. arom. C), 122.6
(CH2CH), 115.1 (quat. arom. C), 114.2 (arom. CH), 62.5
(OCH3), 31.7 (COCH3), 27.3 (CH2CH), 25.7 (CH3), 17.9
(CH3); EI-HRMS Calcd for C14H18O3 (Mþ) 234.1256,
Found 234.1261.
4.4.13. 1-[2-Hydroxy-6-methoxy-3-(3-methylbut-2-enyl)-
phenyl]ethanone 4b. To an acetone solution (20 ml) of
dihydroxyacetophenone 4 (100 mg, 0.45 mmol) were suc-
cessively added potassium carbonate (63 mg, 0.45 mmol)
and dimethyl sulfate (43 ml, 0.45 mmol). Then the solution
was heated under reflux for 5 h. After being cooled at room
temperature, the reaction mixture was filtered and evapor-
ated under reduced pressure. The residue was redissolved in
20 ml of CH2Cl2. The organic layer was washed three times
with 15 ml of water and dried over Na2SO4. After removal
of the solvent, the product was purified by column
chromatography (7% AcOEt/cyclohexane) to yield 4b
(79 mg, 74%), IR (cm21): 3448, 1616, 1426 (CvC),
4.4.16. 2-Acetyl-3-benzyloxy-4-(3-methylbut-2-enyl)phe-
nyl acetate 4h. To an acetone solution (20 ml) of
dihydroxyacetophenone 4a (100 mg, 0.38 mmol) were
successively added benzyl bromide (68 ml, 0.57 mmol)
potassium carbonate (190 mg) and tetrabutylammonium
iodide (211 mg, 0.57 mmol). Then the solution was heated
under reflux for 3 h. After being cooled at room tempera-
ture, the reaction mixture was filtered and evaporated under
reduced pressure. The residue was redissolved in 20 ml of
AcOEt. The organic layer was washed three times with
15 ml of water and dried over Na2SO4. After removal of the
solvent, the product was purified by column chromato-
graphy (10% AcOEt/cyclohexane) to yield 4 h (98 mg,
73%), IR (cm21): 1766, 1700, 1200; 1H NMR (CDCl3,
270 MHz): d 7.43–7.36 (m, 5H arom.), 7.25 (d, 1H arom.,
J¼8.5 Hz), 6.87 (d, 1H arom., J¼8.5 Hz), 5.24 (t, 1H,
CH2CH, J¼7 Hz), 4.83 (s, 2H, OCH2Ph), 3.35 (d, 2H,
CH2CH, J¼7 Hz), 2.52 (s, 3H, COCH3), 2.26 (s, 3H,
OCOCH3), 1.75 (s, 3H, CH3), 1.67 (s, 3H, CH3); 13C NMR
(CDCl3, 67.5 MHz): d 201.4 (COCH3), 169.4 (OCOCH3),
154.0, 145.2, 136.4, 133.6p (4£quat. arom. C), 133.3p
(CHvC(CH3)2), 131.5, 128.6, 128.3, 128.1 (6£arom. CH),
127.3 (quat. arom. C), 121.8 (CH2CH), 118.7 (arom. CH),
77.6 (OCH2Ph), 31.8 (COCH3), 27.7 (CH2CH), 25.7 (CH3),
1
1244; H NMR (CDCl3, 270 MHz): d 13.63 (s, 1H, OH),
7.22 (d, 1H arom., J¼8.5 Hz), 6.33 (d, 1H arom.,
J¼8.5 Hz), 5.30 (t, 1H, CH2CH, J¼7.5 Hz), 3.87 (s, 3H,
OCH3), 3.28 (d, 2H, CH2CH, J¼7.5 Hz), 2.67 (s, 3H,
COCH3), 1.75 (s, 3H, CH3), 1.71 (s, 3H, CH3); 13C NMR
(CDCl3, 67.5 MHz): d 205.3, 162.3, 159.7 (2£quat. arom.
C), 135.4 (arom. CH), 132.9 (CHvC(CH3)2), 122.5 (quat.
arom. C), 122.1 (CH2CH), 110.8 (quat. arom. C), 100.3
(arom. CH), 55.4 (OCH3), 33.6 (COCH3), 27.3 (CH2CH),
25.8 (CH3), 17.7 (CH3); EI-HRMS Calcd for C14H18O3
(Mþ) 234.1256, Found 234.1246.
4.4.14. 2-Acetyl-3-methoxy-4-(3-methylbut-2-enyl)phe-
nyl acetate 4g. To an acetone solution (25 ml) of
dihydroxyacetophenone 4a (125 mg, 0.48 mmol) were
successively added potassium carbonate (100 mg,
0.72 mmol) and dimethyl sulfate (68 ml, 0.72 mmol). Then
the solution was heated under reflux for 2 h. After being
cooled at room temperature, the reaction mixture was
filtered and evaporated under reduced pressure. The residue
was redissolved in 20 ml of CH2Cl2. The organic layer was
washed three times with 15 ml of water and dried over

5102
J.-J. Helesbeux et al. / Tetrahedron 59 (2003) 5091–5104
20.9 (OCOCH3), 17.9 (CH3); EI-HRMS Calcd for
C22H24O4 (Mþ) 352.1675, Found 352.1662.
with 15 ml of water and dried over Na2SO4. Removal of the
solvent under reduced pressure yielded 4f (107 mg, 95%),
IR (cm21): 1706, 1271, 1244; 1H NMR (CDCl3, 270 MHz):
d 7.13 (d, 1H arom., J¼8.5 Hz), 6.63 (d, 1H arom.,
J¼8.5 Hz), 5.25 (t, 1H, CH2CH, J¼7 Hz), 3.79 (s, 3H,
OCH3), 3.73 (s, 3H, OCH3), 3.21 (d, 2H, CH2CH, J¼7 Hz),
2.52 (s, 3H, COCH3), 1.75 (s, 3H, CH3), 1.72 (s, 3H, CH3);
13C NMR (CDCl3, 67.5 MHz): d 203.2 (CvO), 154.9,
154.8 (2£quat. arom. C), 132.7 (CHvC(CH3)2), 130.9
(arom. CH), 127.4, 125.9 (2£quat. arom. C), 122.7
(CH2CH), 106.9 (arom. CH), 62.8, 55.8 (2£OCH3), 32.4
(COCH3), 27.4 (CH2CH), 25.7 (CH3), 17.8 (CH3); EI-
HRMS Calcd for C15H20O3 (Mþ) 248.1413, Found
248.1412.
4.4.17. 1-[2-(Benzyloxy)-6-hydroxy-3-(3-methylbut-2-
enyl)phenyl]ethanone 4d. Monoacetate derivative 4h
(98 mg, 0.28 mmol) was dissolved in a 2:1:1 ratio mixture
(12 ml) of methanol/aqueous saturated NaHCO3 solution/
water. This reaction mixture was stirred at room tempera-
ture for 40 min. Then diluted HCl (10%) was added down to
pH¼2. The resulting mixture was extracted four times with
15 ml of AcOEt. The combined organic layers were washed
with 2£25 ml of water and dried over Na2SO4. After
removal of the solvent under reduced pressure, purification
of the crude product by column chromatography (50%
CH2Cl2/cyclohexane) yielded 4d as a colorless oil (60 mg,
70%), IR (cm21): 3443, 1632, 1468, 1217; 1H NMR
(CDCl3, 270 MHz): d 12.31 (s, 1H, OH), 7.43–7.35 (m, 5H
arom.), 7.32 (d, 1H arom., J¼8.5 Hz), 6.78 (d, 1H arom.,
J¼8.5 Hz), 5.23 (t, 1H, CH2CH, J¼7.5 Hz), 4.85 (s, 2H,
OCH2Ph), 3.32 (d, 2H, CH2CH, J¼7.5 Hz), 2.69 (s, 3H,
COCH3), 1.75 (s, 3H, CH3), 1.67 (s, 3H, CH3); 13C NMR
(CDCl3, 67.5 MHz): d 205.3 (COCH3), 161.4, 157.7
(2£quat. arom. C), 137.3 (arom. CH), 136.3 (quat. arom.
C), 133.3 (CHvC(CH3)2), 128.6, 128.3, 127.4 (5£arom.
CH), 125.6 (quat. arom. C), 122.4 (CH2CH), 115.8 (quat.
arom. C), 114.3 (arom. CH), 77.6 (OCH2Ph), 31.9
(COCH3), 27.4 (CH2CH), 25.7 (CH3), 17.8 (CH3); EI-
HRMS Calcd for C20H22O3 (Mþ) 310.1568, Found
310.1562.
4.5. General procedure for the photooxygenation–
reduction sequence at 2308C
A CH2Cl2 solution (30 ml) of prenylated compound (19a–
19e) (30 mg) and tetraphenylporphine (3 mg, 0.005 mmol),
as the photosensitizer, was cooled at 2308C and then was
irradiated at 2308C with a halogen lamp (500 W). After
total consumption of the starting material, a slight excess of
triphenylphosphine (1.1 equiv.) was added and the resulting
mixture was stirred overnight at 2308C.
4.5.1. 2-Acetyl-3-hydroxy-4-(2-hydroxy-3-methylbut-3-
enyl)phenyl acetate 26a. The typical conditions given in
Section 4.5 were employed, starting with 4a (30 mg,
0.11 mmol). Purification of the crude product by preparative
TLC (20% AcOEt/cyclohexane) yielded 26a as a beige solid
(14 mg, 45%), mp: 90–918C, IR (cm21): 3378, 1756, 1631,
4.4.18. 2-Acetyl-3-acetyloxy-4-(3-methylbut-2-enyl)-
phenyl acetate 4e. To a CH2Cl2 solution (120 ml) of
dihydroxyacetophenone 4 (1 g, 4.54 mmol) were added
triethylamine (2.54 ml, 18.1 mmol) and dropwise a CH2Cl2
solution (3 ml) of acetyl chloride (1.30 ml, 18.1 mmol). The
resulting solution was strirred 4 h at room temperature.
Then the reaction mixture was successively washed with
2£25 ml of water, 2£25 ml of diluted HCl and 2£25 ml of
water. The organic layer was dried over sodium sulfate,
filtered and the solvent was evaporated under reduced
pressure to yield the diacetate derivative 4e as an orange oil
(1.31 g, 95%), IR (cm21): 1767, 1702, 1185; 1H NMR
(CDCl3, 270 MHz): d 7.29 (d, 1H arom., J¼7.5 Hz), 7.01 (d,
1H arom., J¼7.5 Hz), 5.20 (t, 1H, CH2CH, J¼7 Hz), 3.21
(d, 2H, CH2CH, J¼7 Hz), 2.45 (s, 3H, COCH3), 2.28 (s, 3H,
OCOCH3), 2.27 (s, 3H, OCOCH3), 1.75 (s, 3H, CH3), 1.69
(s, 3H, CH3); 13C NMR (CDCl3, 67.5 MHz): d 198.9
(COCH3), 168.7 (2£OCOCH3), 145.7, 145.4, 132.3
(3£quat. arom. C), 134.1 (CHvC(CH3)2), 131.4 (arom.
CH), 128.0 (quat. arom. C), 120.7 (CH2CH), 120.3 (arom.
CH), 30.8 (COCH3), 28.4 (CH2CH), 25.7 (CH3), 21.0, 20.6
(2£OCOCH3), 17.8 (CH3); CI-HRMS Calcd for C17H21O5
([MþH]þ) 305.1389, Found 305.1365.
1
1195; H NMR (CDCl3, 270 MHz): d 13.13 (s, 1H, OH),
7.37 (d, 1H arom., J¼8 Hz), 6.58 (d, 1H arom., J¼8 Hz),
4.99 (br s, 1H, CvCH2), 4.86 (br s, 1H, CvCH2), 4.35 (dd,
1H, CH2CHOH, J¼8.5 Hz, 3.5 Hz), 3.00 (dd, 1H, CH2-
CHOH, J¼14 Hz, 3.5 Hz), 2.78 (dd, 1H, CH2CHOH,
J¼14 Hz, 8.5 Hz), 2.63 (s, 3H, COCH3), 2.38 (s, 3H,
OCOCH3), 1.83 (s, 3H, CH3); 13C NMR (CDCl3,
67.5 MHz): d 203.4 (COCH3), 168.8 (OCOCH3), 161.7,
149.8 (2£quat. arom. C), 147.2 (CH2vC(CH3)), 136.9
(arom. CH), 125.8, 114.0 (2£quat. arom. C), 113.4 (arom.
CH), 110.8 (CH2vC(CH3)), 75.2 (CH2CHOH), 36.4 (CH2-
CHOH), 32.2 (COCH3), 21.6 (OCOCH3), 18.1 (CH3); EI-
HRMS Calcd for C15H18O5 (Mþ) 278.1154, Found
278.1148.
4.5.2. 2-Acetyl-3-hydroxy-4-(3-hydroxy-3-methylbut-1-
enyl)phenyl acetate 27a. The typical conditions given in
Section 4.5 were employed, starting with 4a (30 mg,
0.11 mmol). Purification of the crude product by preparative
TLC (20% AcOEt/cyclohexane) followed by a recristalliza-
tion (AcOEt/hexane) yielded 27a as green cristals (11 mg,
36%), mp: 86–888C, IR (cm21): 3442, 1771, 1627, 1189;
1H NMR (CD3OD, 270 MHz): d 7.60 (d, 1H arom.,
J¼8.5 Hz), 6.90 (s, 1H, ArCH¼CH, J¼16 Hz), 6.60 (d,
1H arom., J¼8.5 Hz), 6.41 (d, 1H, ArCH¼CH, J¼16 Hz),
2.62 (s, 3H, COCH3), 2.36 (s, 3H, OCOCH3), 1.38 (s, 6H,
2£CH3); 13C NMR (CD3OD, 67.5 MHz): d 205.2 (COCH3),
170.6 (OCOCH3), 161.1, 151.7 (2£quat. arom. C), 140.1
(ArCHvCH), 132.8 (arom. CH), 125.8 (quat. arom. C),
120.5 (ArCH¼CH), 115.8 (quat. arom. C), 115.2 (arom.
CH), 71.6 (C(CH3)2), 32.5 (COCH3), 29.9 (2£CH3), 21.4
4.4.19. 1-[2,6-Dimethoxy-3-(3-methylbut-2-enyl)phenyl]-
ethanone 4f. To an acetone solution (20 ml) of dihydroxy-
acetophenone 4 (100 mg, 0.45 mmol) were successively
added potassium carbonate (226 mg, 1.63 mmol) and
dimethyl sulfate (1.2 ml, 1.81 mmol). Then the solution
was heated under reflux for 5 h. After being cooled at room
temperature, the reaction mixture was filtered and evapor-
ated under reduced pressure. The residue was redissolved in
20 ml of CH2Cl2. The organic layer was washed three times

J.-J. Helesbeux et al. / Tetrahedron 59 (2003) 5091–5104
5103
(OCOCH3); EI-HRMS Calcd for C15H18O5 (Mþ) 278.1154,
Found 278.1124.
(30 mg, 0.13 mmol). Purification of the crude product by
preparative TLC (40% AcOEt/cyclohexane) yielded 27c as
a colorless oil (13 mg, 41%), IR (cm21): 3423, 1627, 1219;
1H NMR (CD3OD, 270 MHz): d 7.58 (d, 1H arom.,
J¼8.5 Hz), 6.76 (s, 1H, ArCH¼CH, J¼16 Hz), 6.69 (d,
1H arom., J¼8.5 Hz), 6.28 (d, 1H, ArCHvCH, J¼16 Hz),
3.77 (s, 3H, OCH3), 2.68 (s, 3H, COCH3), 1.38 (s, 6H,
2£CH3); 13C NMR (CD3OD, 67.5 MHz): d 206.3 (COCH3),
162.0, 159.7 (2£quat. arom. C), 138.7 (ArCHvCH), 133.7
(arom. CH), 129.9, 123.5 (2£quat. arom. C), 121.2
(ArCHvCH), 114.8 (arom. CH), 71.6 (C(CH3)2), 63.2
(OCH3), 32.3 (COCH3), 30.0 (2£CH3); EI-HRMS Calcd for
C14H18O4 (Mþ) 250.1205, Found 250.1202.
4.5.3. 1-[2-Hydroxy-3-(2-hydroxy-3-methylbut-3-enyl)-
6-methoxyphenyl]ethanone 26b. The typical conditions
given in Section 4.5 were employed, starting with 4b
(30 mg, 0.13 mmol). Purification of the crude product by
preparative TLC (20% AcOEt/cyclohexane) yielded 26b as
a colorless oil (13 mg, 40%), IR (cm21): 3443, 1610, 1247;
1H NMR (CDCl3, 270 MHz): d 13.81 (s, 1H, OH), 7.28 (d,
1H arom., J¼8.5 Hz), 6.37 (d, 1H arom., J¼8.5 Hz), 4.98
(br s, 1H, CvCH2), 4.84 (br s, 1H, CvCH2), 4.32 (dd, 1H,
CH2CHOH, J¼8.5 Hz, 4 Hz), 3.90 (s, 3H, OCH3), 2.94 (dd,
1H, CH2CHOH, J¼14 Hz, 4 Hz), 2.74 (dd, 1H, CH2CHOH,
J¼14 Hz, 8.5 Hz), 2.69 (s, 3H, COCH3), 1.83 (s, 3H,
CH3); 13C NMR (CDCl3, 67.5 MHz): d 205.5 (COCH3),
162.5, 160.3 (2£quat. arom. C), 147.4 (CH2vC(CH3)),
137.6 (arom. CH), 119.5, 110.9 (2£quat. arom. C), 110.5
(CH2vC(CH3)), 100.7 (arom. CH), 75.5 (CH2CHOH), 55.5
(OCH3), 36.2 (CH2CHOH), 33.6 (COCH3), 18.2 (CH3);
EI-HRMS Calcd for C14H18O4 (Mþ) 250.1205, Found
250.1209.
4.5.7. 1-[2-(Benzyloxy)-6-hydroxy-3-(2-hydroxy-3-
methylbut-3-enyl)phenyl]ethanone 26d. The typical con-
ditions given in Section 4.5 were employed, starting with 4d
(30 mg, 0.10 mmol). Purification of the crude product by
preparative TLC (30% AcOEt/cyclohexane) followed by a
recristallization (AcOEt/hexane) yielded 26d as green
cristals (11 mg, 35%), mp: 56–578C, IR (cm21): 3312,
1
1627, 1472, 1364, 1226; H NMR (CDCl3, 270 MHz): d
12.20 (s, 1H, OH), 7.41–7.37 (m, 6H arom.), 6.80 (d, 1H
arom., J¼8.5 Hz), 4.94 (br s, 1H, CvCH2), 4.89 (s, 1H,
OCH2Ph), 4.87 (s, 1H, OCH2Ph), 4.84 (br s, 1H, CvCH2),
4.32 (dd, 1H, CH2CHOH, J¼8.5 Hz, 5 Hz), 2.83 (dd, 1H,
CH2CHOH, J¼14 Hz, 5 Hz), 2.75 (dd, 1H, CH2CHOH,
J¼14 Hz, 8.5 Hz), 2.71 (s, 3H, COCH3), 1.75 (s, 3H, CH3);
13C NMR (CDCl3, 67.5 MHz): d 205.1 (COCH3), 161.8,
158.4 (2£quat. arom. C), 147.0 (CH2vC(CH3)), 138.2
(arom. CH), 136.0 (quat. arom. C), 128.7, 128.5, 127.6
(5£arom. CH), 122.7, 116.1 (2£quat. arom. C), 114.5
(arom. CH), 111.2 (CH2vC(CH3)), 78.2 (OCH2Ph), 76.0
(CH2CHOH), 35.8 (CH2CHOH), 31.6 (COCH3), 17.9
(CH3); EI-HRMS Calcd for C20H22O4 (Mþ) 326.1518,
Found 326.1529.
4.5.4. 1-[2-Hydroxy-3-(3-hydroxy-3-methylbut-1-enyl)-
6-methoxyphenyl]ethanone 27b. The typical conditions
given in Section 4.5 were employed, starting with 4b
(30 mg, 0.13 mmol). Purification of the crude product by
preparative TLC (20% AcOEt/cyclohexane) yielded 27b as
a colorless oil (11 mg, 34%), IR (cm21): 3357, 1610, 1251;
1H NMR (CD3OD, 270 MHz): d 7.61 (d, 1H arom.,
J¼8.5 Hz), 6.83 (s, 1H, ArCH¼CH, J¼16 Hz), 6.55 (d,
1H arom., J¼8.5 Hz), 6.29 (d, 1H, ArCHvCH, J¼16 Hz),
3.92 (s, 3H, OCH3), 2.65 (s, 3H, COCH3), 1.37 (s, 6H,
2£CH3); 13C NMR (CD3OD, 67.5 MHz): d 206.9 (COCH3),
162.5, 162.4 (2£quat. arom. C), 137.6 (ArCHvCH), 134.4
(arom. CH), 120.9 (ArCHvCH), 120.2, 111.9 (2£quat.
arom. C), 102.7 (arom. CH), 71.7 (C(CH3)2), 56.2 (OCH3),
33.9 (COCH3), 30.0 (2£CH3); EI-HRMS Calcd for
C14H18O4 (Mþ) 250.1205, Found 250.1205.
4.5.8. 1-[2-(Benzyloxy)-6-hydroxy-3-(3-hydroxy-3-
methylbut-1-enyl)phenyl]ethanone 27d. The typical con-
ditions given in Section 4.5 were employed, starting with 4d
(30 mg, 0.13 mmol). Purification of the crude product by
preparative TLC (30% AcOEt/cyclohexane) followed by a
recristallization (AcOEt/hexane) yielded 27d as yellow
needles (16 mg, 51%), IR (cm21): 3415, 1631, 1366, 1218;
1H NMR (CD3OD, 270 MHz): d 7.59 (d, 1H arom.,
J¼9 Hz), 7.43–7.36 (5H arom.), 6.81 (s, 1H, ArCH¼CH,
J¼16 Hz), 6.72 (d, 1H arom., J¼9 Hz), 6.29 (d, 1H,
ArCHvCH, J¼16 Hz), 4.89 (s, 2H, OCH2Ph), 2.58 (s,
3H, COCH3), 1.33 (s, 6H, 2£CH3); 13C NMR (CD3OD,
67.5 MHz): d 206.2 (COCH3), 161.2, 157.7 (2£quat. arom.
C), 138.8 (ArCHvCH), 133.2 (quat. arom. C), 133.1
(arom. CH), 129.6, 129.4, 129.3 (5£arom. CH), 123.8 (quat.
arom. C), 121.4 (ArCHvCH), 119.8 (quat. arom. C), 114.8
(arom. CH), 78.5 (OCH2Ph), 71.5 (C(CH3)2), 32.6
(COCH3), 29.2 (2£CH3); EI-HRMS Calcd for C20H22O4
(Mþ) 326.1518, Found 326.1503.
4.5.5. 1-[6-Hydroxy-3-(2-hydroxy-3-methylbut-3-enyl)-
2-methoxyphenyl]ethanone 26c. The typical conditions
given in Section 4.5 were employed, starting with 4c
(30 mg, 0.13 mmol). Purification of the crude product by
preparative TLC (40% AcOEt/cyclohexane) yielded 26c as
a colorless oil (9 mg, 29%), IR (cm21): 3444, 1628, 1585,
1
1220; H NMR (CDCl3, 270 MHz): d 12.38 (s, 1H, OH),
7.07 (d, 1H arom., J¼8.5 Hz), 6.40 (d, 1H arom.,
J¼8.5 Hz), 4.98 (br s, 1H, CvCH2), 4.87 (br s, 1H,
CvCH2), 4.31 (dd, 1H, CH2CHOH, J¼8.5 Hz, 4.5 Hz),
3.79 (s, 3H, OCH3), 2.87 (dd, 1H, CH2CHOH, J¼14 Hz,
4.5 Hz), 2.78 (dd, 1H, CH2CHOH, J¼14 Hz, 8.5 Hz), 2.76
(s, 3H, COCH3), 1.83 (s, 3H, CH3); 13C NMR (CDCl3,
67.5 MHz): d 205.0 (COCH3), 162.2, 160.0 (2£quat.
arom. C), 147.0 (CH2vC(CH3)), 138.3 (arom. CH),
122.3, 115.3 (2£quat. arom. C), 114.4 (arom. CH), 111.2
(CH2vC(CH3)), 76.0 (CH2CHOH), 62.9 (OCH3), 35.6
(CH2CHOH), 31.4 (COCH3), 18.0 (CH3); EI-MS m/z 250
(Mþ,6) 179 (100), 165 (16), 121 (16), 77 (19), 43 (30).
4.5.9. 2-Acetyl-3-acetyloxy-4-(2-hydroxy-3-methylbut-3-
enyl)phenyl acetate 26e. The typical conditions given in
Section 4.5 were employed, starting with 4e (30 mg,
0.11 mmol). Purification of the crude product by preparative
TLC (35% AcOEt/cyclohexane) yielded 26e as a colorless
4.5.6. 1-[6-Hydroxy-3-(3-hydroxy-3-methylbut-1-enyl)-
2-methoxyphenyl]ethanone 27c. The typical conditions
given in Section 4.5 were employed, starting with 4c
1
oil (8 mg, 26%), IR (cm21): 1767, 1700, 1369, 1186; H

5104
J.-J. Helesbeux et al. / Tetrahedron 59 (2003) 5091–5104
NMR (CDCl3, 270 MHz): d 7.41 (d, 1H arom., J¼8.5 Hz),
7.06 (d, 1H arom., J¼8.5 Hz), 4.99 (br s, 1H, CvCH2), 4.88
(br s, 1H, CvCH2), 4.24 (dd, 1H, CH2CHOH, J¼9 Hz,
4 Hz), 2.80 (dd, 1H, CH2CHOH, J¼14 Hz, 4 Hz), 2.69 (dd,
1H, CH2CHOH, J¼14 Hz, 9 Hz), 2.46 (s, 3H, COCH3),
2.30 (s, 3H, OCOCH3), 2.29 (s, 3H, OCOCH3), 1.80 (s, 3H,
CH3); 13C NMR (CDCl3, 67.5 MHz): d 198.9 (COCH3),
169.1, 168.6 (2£OCOCH3), 146.8p (CH2vC(CH3)),
146.3p, 145.9 (2£quat. arom. C), 132.9 (arom. CH),
129.6, 128.2 (2£quat. arom. C), 120.4 (arom. CH), 111.3
(CH2vC(CH3)), 75.2 (CH2CHOH), 36.3 (CH2CHOH),
31.0 (COCH3), 21.0, 20.7 (2£OCOCH3), 17.9 (CH3);
EI-HRMS Calcd for C17H20O6 (Mþ) 320.1260, Found
320.1255.
EI-HRMS Calcd for C15H20O4 (Mþ) 264.1362, Found
264.1359.
4.5.12. 1-[3-(3-Hydroxy-3-methylbut-1-enyl)-2,6-
dimethoxyphenyl]ethanone 27f. The typical conditions
given in Section 4.5 were employed, starting with 4f
(30 mg, 0.12 mmol). Purification of the crude product by
preparative TLC (30% AcOEt/cyclohexane) yielded 27f as
a colorless oil (18 mg, 55%), IR (cm21): 3445, 1704, 1244;
1H NMR (CD3OD, 270 MHz): d 7.41 (d, 1H arom.,
J¼9 Hz), 6.71 (d, 1H arom., J¼8.5 Hz), 6.67 (s, 1H,
ArCH¼CH, J¼16 Hz), 6.29 (d, 1H, ArCHvCH, J¼16 Hz),
3.81 (s, 3H, OCH3), 3.72 (s, 3H, OCH3), 2.50 (s, 3H,
COCH3), 1.43 (s, 6H, 2£CH3); 13C NMR (CD3OD,
67.5 MHz): d 202.8 (COCH3), 155.8, 154.5 (2£quat.
arom. C), 137.7 (ArCHvCH), 128.1 (arom. CH), 128.1,
123.5 (2£quat. arom. C), 120.0 (ArCHvCH), 107.2 (arom.
CH), 71.1 (C(CH3)2), 63.0 (OCH3), 55.8 (OCH3), 32.4
(COCH3), 29.6 (2£CH3); EI-HRMS Calcd for C15H20O4
(Mþ) 264.1362, Found 264.1350.
4.5.10. 2-Acetyl-3-acetyloxy-4-(3-hydroxy-3-methylbut-
1-enyl)phenyl acetate 27e. The typical conditions given
in Section 4.5 were employed, starting with 4e (30 mg,
0.11 mmol). Purification of the crude product by preparative
TLC (35% AcOEt/cyclohexane) yielded 27e as a colorless
1
oil (14 mg, 45%), IR (cm21): 1767, 1702, 1369, 1187; H
NMR (CD3OD, 270 MHz): d 7.69 (d, 1H arom., J¼8.5 Hz),
7.10 (d, 1H arom., J¼8.5 Hz), 6.58 (s, 1H, ArCH¼CH,
J¼16 Hz), 6.41 (d, 1H, ArCHvCH, J¼16 Hz), 2.42 (s, 3H,
COCH3), 2.29 (s, 3H, OCOCH3), 2.26 (s, 3H, OCOCH3),
1.36 (s, 6H, 2£CH3); 13C NMR (CD3OD, 67.5 MHz): d
200.8 (COCH3), 170.6 (2£OCOCH3), 148.1, 146.1 (2£quat.
arom. C), 143.2 (ArCHvCH), 130.6, 129.9 (2£quat. arom.
C), 129.5 (arom. CH), 122.2 (ArCHvCH), 119.7 (arom.
CH), 71.6 (C(CH3)2), 31.3 (COCH3), 29.9 (2£CH3), 20.7,
20.5 (2£OCOCH3); EI-HRMS Calcd for C17H20O6 (Mþ)
320.1260, Found 320.1258.
Acknowledgements
´
This research was supported by a grant from Departement
du Maine-et-Loire (France).
References
´
´
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4.5.11. 1-[3-(2-Hydroxy-3-methylbut-3-enyl)-2,6-
dimethoxyphenyl]ethanone 26f. The typical conditions
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(30 mg, 0.12 mmol). Purification of the crude product by
preparative TLC (30% AcOEt/cyclohexane) yielded 26f as
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J¼8.5 Hz), 6.66 (d, 1H arom., J¼8.5 Hz), 4.98 (br s, 1H,
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67.5 MHz): d 203.0 (COCH3), 155.4, 155.3 (2£quat.
arom. C), 147.1 (CH2vC(CH3)), 132.3 (arom. CH),
125.8, 124.2 (2£quat. arom. C), 110.8 (CH2vC(CH3)),
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